The cyclosporins comprise a class of structurally distinctive, cyclic, poly-N-methylated undecapeptides, commonly possessing pharmacological activity, in particular immunosuppressive, anti-inflammatory or anti-parasitic activity. The first of the cyclosporins to be isolated was the naturally occurring fungal metabolite cyclosporin, Cyclosporin A represented as follows: 
Since the original discovery of cyclosporin, a wide variety of naturally occurring cyclosporins have been isolated and identified, and many further non-natural cyclosporins have been prepared by total- or semi-synthetic means or by the application of modified culture techniques. The class comprising cyclosporins is thus now substantial and includes, for example, the naturally occurring Cyclosporins A through Z for example, [Thr]2[Val]2, [Nva]2 and [Nva]2-, [Nva]5 -Cyclosporin (also known as Cyclosporins C, D, G and M respectively), [(D)MeVal]11-Cyclosporin (also known as Cyclosporin H), [cf., Traber et al.;1, Helv. Chim. Acta, 60, 1247-1255 (1977); Traber et al.; 2, Helv. Chim. Acta, 65, 1655-1667 (1982); Kobel et al.; Europ. J. Applied Microbiology and Biotechnology, 14, 273-240 1982); and Von Wartburg et al.; Progress in Allergy, 38, 28-45, 1986)]; as well as various non-natural cyclosporin derivatives and artificial or synthetic cyclosporin derivatives and artificial or synthetic cyclosporins including dihydrocyclosporins [in which the MeBmt-residue is saturated by hydrogenation]; derivatized cyclosporins (e.g., in which the 3′-O-atom of the MeBmt- residue is acylated or a further substituent is introduced at the α-carbon atom of the sarcosyl residue at the 3-position); and cyclosporins in which variant amino acids are incorporated at specific positions within the peptide sequence, for example, [3-O-acetyl-MeBmt]1-Cyclosporin (also known as Dihydro-cyclosporin D), [(D)Ser]8Cyclosporin, [Melle]11-Cyclosporin, [MeAla]6-Cyclosporin, [(D) Pro]3-Cyclosporin etc., employing the total synthetic method for the production of cyclosporins developed by R. Wenger—see e.g. Traber et al., 1; Traber et al., 2; and Kobel et al., loc cit. U.S. Pat. Nos. 4,108,985, 4,220,641, 4,288,431, 4,554,351, 4,396,542 and 4,798,823; European Patent Publication Nos. 34,567A, 56,782A, 300,784A and 300,785; International Patent Publication No. WO 86/02080 and UK Patent Publication Nos. 2,206,119 and 2,207,678; Wenger 1, Transpl. Proc., 15 Suppl. 1:2230 (1983); Wenger 2, Angew. Chem. Int. Ed. 24 77 (1985) and Wenger 3, Progress in the Chemistry of Organic Natural Products, 50,123 (1986).
The compound cyclosporine (cyclosporine A or CsA) has found wide use since its introduction in the fields of organ transplantation and immunomodulation, and has brought about a significant increase in the success rate for transplantation procedures. Side effects with systemic CsA include increase in diastolic blood pressure, decrease in renal function, hepatic dysfunction, hypertrichosis, tremor, gingival hyperplasis, and paraesthsia. The systemic toxicity of CsA limits its use for the treatment of certain diseases. It is therefore desirable to find immunosuppresant compounds with improved systemic efficacy and safety.